This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESIS Histone deacytelase inhibitors (HDAC) will have antitumor activity in a variety of childhood tumors. SPECIFIC AIMS Primary Aim: To define and describe the toxicities of oral valproic acid (VPA) administered twice daily at does required to maintain serum trough concentrations of 100-150 mcg/ml or 150-200 mcg/ml in children with recurrent or refractory solid tumors, including CNS tumors. Secondary Aims: To measure the steady state serum trough concentration of free VPA at the targeted total trough VPA concentrations. To evaluate the prhamacokinetic profile of twic daily VPA administration in children. To evaluate the steady state histone acetylation status of peripheral blood monocytes at the targeted trough VPA concentrations. To investigate potential correlations between histone acetylation and free or total VPA trough concentrations. To preliminarily define the antitumor activity of VPA within the confines of a Phase 1 trial.